Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05×10⁻²³) and class II molecules (P=4.50×10⁻³⁴), PTPN22 (P=1.31×10⁻⁷), LPP (P=1.01×10⁻¹¹), IL2RA (P=2.78×10⁻⁹), UBASH3A (P=1.26×10⁻⁹), and C1QTNF6 (P=2.21×10⁻¹⁶). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07×10⁻¹⁵) and GZMB (P=3.44×10⁻⁸), and in a locus containing TYR (P=1.60×10⁻¹⁸), encoding tyrosinase. We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma.

Richard Spritz and colleagues report genome-wide association analyses identifying 13 new susceptibility loci for generalized vitiligo. Their functional pathway analysis shows that many vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components. We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10−8), MC1R (P = 1.82 × 10−13), a region near TYR (P = 1.57 × 10−13), IFIH1 (P = 4.91 × 10−15), CD80 (P = 3.78 × 10−10), CLNK (P = 1.56 × 10−8), BACH2 (P = 2.53 × 10−8), SLA (P = 1.58 × 10−8), CASP7 (P = 3.56 × 10−8), CD44 (P = 1.78 × 10−9), IKZF4 (P = 2.75 × 10−14), SH2B3 (P = 3.54 × 10−18) and TOB2 (P = 6.81 × 10−10). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration.

Regulatory T cells (Tregs) are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. Given the crucial role of Tregs in maintaining immune homeostasis, it is probably not surprising that many microbial species and their metabolites have the potential to induce Tregs. There is now great interest in the therapeutic potential of probiotics and prebiotics based strategies for a range of autoimmune disorders. This review will summarise recent findings concerning the role of probiotics and prebiotics in induction of Tregs to ameliorate the autoimmune conditions. In addition, the article is focused to explain the different mechanisms of Treg induction and function by these probiotics and prebiotics, based on the available studies till date. The article further proposes that induction of Tregs by probiotics and prebiotics could lead to the development of new therapeutic approach towards curbing the autoimmune response and as an alternative to detrimental immunosuppressive drugs.

Abstract:  The pathobiology of vitiligo has been hotly disputed for as long as one remembers, and has been a magnet for endless speculation. Evidently, the different schools of thought – ranging, e.g. from the concept that vitiligo essentially is a free‐radical disorder to that of vitiligo being a primary autoimmune disease – imply very different consequences for the best therapeutic strategies that one should adopt. As a more effective therapy for this common, often disfiguring pigmentary disorder is direly needed, we must strive harder to settle the pathogenesis debate definitively – on the basis of sound experimental evidence, rather than by a war of dogmatic theories.Recognizing, however, that it is theories which tend to guide our experimental designs and choice of study parameters, the various pathogenesis theories on the market deserve to be critically, yet unemotionally re‐evaluated. This Controversies feature invites you to do so, and to ask yourself: Is there something important or worthwhile exploring in other pathogenesis scenarios than those already favoured by you that may help you improve your own study design, next time you have a fresh look at vitiligo?Vitiligo provides a superb model for the study of many fundamental problems in skin biology and pathology. Therefore, even if it later turns out that, as far as your own vitiligo pathogenesis concept is concerned, you have barked‐up the wrong tree most of the time, chances are that you shall anyway have generated priceless new insights into skin function along the way.